5-Chloro-2,4-dihydroxypyridine (non-proprietary name: Gimeracil) is known to potentiate the anti-tumor activity of 5-fluorouracil (an anti-malignant-tumor agent) by inhibiting dihydropyrimidine dehydrogenase, which is a biodegradation enzyme which acts on 5-fluorouracil (see Patent Document 1). As a commercial product, a 5-fluorouracil-based anti-tumor agent, which is a combination drug of Gimeracil, Tegafur, and Oteracil Potassium, is available on the market as TS-1 (trade name).
Hitherto, the following 5-chloro-2,4-dihydroxypyridine production processes are known. Note that, in the following schemes, symbols “Ac” and “Et” denote an acetyl group and an ethyl group, respectively.
A process disclosed in Non-Patent Document 1 includes a step performed under very severe conditions (i.e., under acidic conditions, in an autoclave at 200° C.), which makes the process industrially unsuitable.

A process disclosed in Non-Patent Document 2 includes a large number of steps, which make the process difficult to carry out on an industrial scale.

Patent Document 2 discloses a process in which an α, β-unsaturated keto ester derivative is synthesized from malonyl dichloride, and ammonia is reacted with the ester derivative, to thereby produce 2,4-dihydroxy-5-halogenopyridine derivative. In this process, handling of starting materials for producing the α, β-unsaturated keto ester derivative serving as an intermediate is problematic, and there are some problems associated with reaction conditions. For the above reasons the process is difficult to be employed on an industrial scale.

Patent Document 3 discloses a process in which the 5-position of 3-cyano-2-hydroxy-3-methoxypiridine is selectively halogenized, and the cyano group is removed through hydrolysis/decarbonation by use of strong acid with heating, to thereby produce 2,4-dihydroxy-5-halogenopyridine derivative. In this method, a large amount of strong acid is employed for hydrolysis, and a large amount of base is employed for neutralizing the strong acid. As a result, a large amount of salts are formed as industrial wastes, which are not preferred from the viewpoint of the environment.
    [Patent Document 1] Japanese Patent Application Laid-Open (kokai) No. 62-155215    [Patent Document 2] Japanese Patent Application Laid-Open (kokai) No. 5-39241    [Patent Document 3] Japanese Patent Application Laid-Open (kokai) No. 5-78324    [Non-Patent Document 1] Recueil Des Travaux Chemiques Des Pays-Bas, 1954, Vol. 73, p. 704    [Non-Patent Document 2] Recueil Des Travaux Chemiques Des Pays-Bas, 1953, Vol. 72, p. 285